Administration of Allogenic UC-MSCs as Adjuvant Therapy for Critically-Ill COVID-19 Patients
Status:
Recruiting
Trial end date:
2020-09-01
Target enrollment:
Participant gender:
Summary
Novel Coronavirus (2019nCoV) or Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)
that causes Coronavirus Disease 2019, or known as Covid-19 has recently become a global
health emergency since it was first detected in Wuhan, the People Republic of China in
December 2019. Since then, the prevalence has rapidly increased worldwide. In Indonesia, by
the end of April 2020, around 10,000 patients have been tested positive for Covid-19
infection, with a case fatality rate of around 8%.
The pathogenesis of Covid-19 is still under investigation and to our understanding, ACE2
receptors in the alveoli serve as the binding site of the S-protein of envelope spike virus
of SARS-CoV-2. TMPRSS2 enzyme aids the fusion between cell membrane and capsid of the virus,
allowing penetration of virus into the cell. Vesicles containing virion fuse with cell
membrane and released as new virions. Cytopathic effect of the virus and its ability to
overcome immune response determines the degree of infection.
Differences in immunological profile among degrees of severity of Covid-19 may vary
especially for the number of pro-inflammatory cytokines such as tumor necrosis factor alpha
(TNF-α), interleukin (IL)-1, IL-6, IL-8, leukemia-inhibiting factors (LIF), immunological
markers such as CXCR3+CD4+, CXCR3+CD8+ T cell and CXCR3+ NK cells, implying the ongoing
cytokine storm. The previous studies also found increasing number for infection markers such
as procalcitonin, ferritin, and C-reactive protein. The decreasing number of
anti-inflammatory cytokines in such as IL-10 also supports this finding.
Previous studies have shown immunomodulating and anti-inflammatory capacity of the
mesenchymal stem cells (MSCs). MSCs contributed to the shifting of pro-inflammatory Th2 into
anti-inflammatory Th2. One of the most recent study on the usage of MSCs on Covid-19 patients
showed increased expression of leukemia inhibitory factor (LIF), which give rise to
inhibitory effect of T lymphocyte and natural killer (NK) cell population. Vascular
epithelial growth factor (VEGF) is found increasing following MSCs administration, which
indicates the ability to improve the disrupted capillaries due to SARS-Cov-2 infection. The
ability of MSCs in differentiating to alveolar cells is proven by the presence of SPM and
SPC2, surfactant proteins produced by type II alveolar cells. MSCs are unable to be infected
by SARS-CoV-2 since they don't have ACE2 receptors and TMPRSS2 enzyme.